Efficacy of CRISPR-Cas9 CAR T-Cell Therapy vs. Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia
Bibliographic record
Abstract
Introduction: With immunotherapy drugs such as Blinatumomab (Blincyto), the current overall survival rate of relapsed/refractory B Lymphocyte Acute Lymphoblastic Leukemia (B-ALL) is 7.8 months in adults. However, with CRISPR-Cas9 gene editing, CAR T-cell therapy may extend survival. By knocking out T-cell receptors (TCRs) and HLA class I receptors on T-cells, CRISPR-Cas9 edited CAR T-cells could become a universal treatment alternative for B-ALL. This study compares the efficacy of CRISPR-Cas9 edited CAR T-cell therapy, a new era of CAR T-cell therapy, to the treatment of relapsed/ refractory B-ALL with Blinatumomab in mice. Methods: A cohort of 30 NSG mice receiving xenografts from an 18-24 year old patient with relapsed B-ALL will be randomly assigned to one of three groups, where they will receive treatment with: (1) mock transduced T-cells, (2) Blincyto, or (3) CRISPR-Cas9 edited TRAC- and B2M- knockout CAR T-cells. Another cohort of 30 NSG mice, receiving human skin xenografts from a healthy donor, will also be assigned to one of the groups and treated accordingly. Tumour shrinkage will be analyzed through in vivo antibody fluorescent imaging in the first cohort. Graft Vs Host Disease (GvHD) development will be assessed in the second cohort. Results: It is expected that mice treated with CRISPR-Cas9 edited CAR T-cells will be more effective at eliminating tumours. Compared to mice treated with Blincyto or mock-transfused T-cells, these mice will exhibit the highest overall response rates, complete response rates and tumour shrinkage rates, and the lowest relapse rates. It is also expected that these mice will not develop GvHD. Discussion: The use of CRISPR-Cas9 edited CAR T-cells in the treatment of B-ALL reveals a new facet to cancer therapeutics. The efficacy of this treatment will be demonstrated through greater tumour shrinkage rates and higher overall response rates than treatment with Blincyto, the current standard treatment drug for B-ALL. Conclusion: Current treatments involving Blinatumomab or conventional CAR T-cell therapy are expensive and therefore inaccessible to many. These results could demonstrate that CRISPR-Cas9 edited CAR T-cell therapy is viable as a safe, universal and more affordable alternative for relapsed/refractory B-ALL treatment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".